From the Department of Veterans Affairs Medical Center, Seattle, Washington; the University of Washington, Seattle, Washington; the Northwest Lipid Research Center, Seattle, Washington; and the Salk Institute, La Jolla, California. For current author addresses, see end of text.

Grant Support: By National Institutes of Health (NIH) grants P50-HD12629, HD00890-01, K0800890-01, and HD13527; the Clinical Research Center of the University of Washington, supported by NIH grant RR-37; the Clinical Nutrition Research Unit, supported by NIH grant DK35816; the Contraceptive Research and Development Agency, and the Department of Veterans Affairs.

Abstract

▪ Objective: To investigate the role of physiologic levels of testosterone in the control of lipoproteins in healthy men.

▪ Design: A double-blind, randomized study.

▪ Setting: A university community.

▪ Participants: Fifteen healthy men, ages 20 to 36 years.

▪ Intervention: We induced acute, reversible hypogonadism in five normal men by administering daily subcutaneous injections of the gonadotropin-releasing-hormone (GnRH) antagonist, Nal-Glu, for 6 weeks. Another group of five normal men received Nal-Glu plus weekly injections of testosterone enanthate, 100 mg/wk, thereby maintaining normal serum testosterone levels. Five additional men received placebo injections.

▪ Results: At the end of the treatment period, HDL cholesterol levels in men receiving Nal-Glu increased by 26% (95% Cl, 18% to 34%; P < 0.05). Levels of HDL2, HDL3, and apoprotein A1 increased by 63% (Cl, 16% to 110%), 17% (Cl, 3% to 31%), and 17% (Cl, 5% to 29%), respectively (P < 0.05 for each parameter). Total cholesterol increased by 12% (Cl, 2% to 22%). Low-density lipoprotein (LDL) cholesterol and triglyceride concentrations did not change. No statistically significant changes occurred in any lipid measurement in men receiving Nal-Glu plus androgen replacement or placebo (P > 0.05).

▪ Conclusions: Experimental hypogonadism induced by administration of a GnRH antagonist results in a statistically significant increase in HDL cholesterol, including HDL2 and HDL3. These effects are most likely due to decreased androgen levels because they are reversed by administration of antagonist together with testosterone. Our results imply that androgen levels in the normal adult male range have a suppressive effect on HDL cholesterol concentration and may contribute to the increased risk for coronary artery disease in men.